Clinical Scenario

Mrs Howe has brought in Daisy, a 5 year old female neutered Domestic Shorthair, for a booster vaccination and health check as she is going into the local cattery in a couple of weeks while Mrs Howe is away on holiday. Daisy is generally well, healthy and happy at home, however Mrs Howe comments that last time Daisy went into the cattery, the cattery owners mentioned that she seemed rather anxious and stressed during her stay. Mrs Howe is keen to make Daisy’s next stay in the cattery as stress free as possible and wonders whether there is anything she can give Daisy temporarily to keep her anxiety to a minimum. You recently picked up a leaflet about alpha-casozepine (Zylkene) at a conference and wondered whether this might help manage Daisy’s anxiety during her cattery stay…

3-Part Question (PICO)

In [cats demonstrating signs of anxiety/fear] does the use of [alpha-casozepine versus placebo] lead to [better management of signs of anxiety/fear]?

Search Strategy and Summary of Evidence

Search Strategy

MEDLINE(R) In-Process & Other Non-Indexed Citations and MEDLINE(R) 1946 to Present using the OVID interface

(cat.mp. OR cats.mp. OR feline.mp. OR felines.mp. OR felis.mp. OR exp Cats/ OR exp Felis/)

AND

(anxiety.mp. OR anxious.mp. OR fearful.mp. OR fear.mp. OR fearfulness.mp. OR stress.mp. OR stressed.mp. OR stressful.mp. OR nervous.mp. OR frightened.mp. OR exp Anxiety/ OR exp Anxiety Disorders/ OR exp Fear/ OR exp Stress, Psychological/)

AND

(alpha casozepine.mp. OR zylkene.mp. OR milk protein.mp. OR lactium.mp. OR casein.mp. OR exp Caseins/ OR exp Milk Proteins/)

CAB Abstracts 1910 to Present using the OVID interface

(cat.mp. OR cats.mp. OR feline.mp. OR felines.mp. OR felis.mp. OR exp cats/ OR exp Felis/)

AND

(anxiety.mp. OR anxious.mp. OR fearful.mp. OR fear.mp. OR fearfulness.mp. OR stress.mp. OR stressed.mp. OR stressful.mp. OR nervous.mp. OR frightened.mp. OR exp anxiety/ OR exp fearfulness/ OR exp stress/)

AND

(alpha casozepine.mp. OR zylkene.mp. OR milk protein.mp. OR lactium.mp. OR casein.mp. OR exp milk protein/ OR exp casein/ OR exp casein hydrolysate/ OR exp alpha-casein/)

Total relevant papers

1 relevant papers from both MEDLINE and CAB Abstracts

Summary of Evidence

Beata et al. (2007) Europe

Title:

Effect of alpha-casozepine (Zylkene) on anxiety in cats

Patient group:

34 cats of various breeds were recruited by certified veterinary behaviourists in general or specialist veterinary practices across Europe. Cats were recruited if they had a score of <15, or had scored 0 in one of the five categories, on a cat behavioural scale. The cats were assigned to two groups: 17 received alpha-casozepine and 17 received a placebo.

Study Type:

Randomised controlled trial

Outcomes:

Overall score on the behavioural scale

Number of the 5 categories scoring 0 on the behaviour scale

Subjective owner assessment of improvement in behaviour

Treatment success: defined as cats where 3 criteria were met (overall score on behavioural scale equal to or greater than 16, no categories scoring 0 on behavioural scale, owner assessent equal to or greater than 6/10)

Individual categories within the behavioural score e.g. relationships with familiar/non-familiar people, fear and autonomic signs, were also examined individually

Key Results:

Behavioural score at 56 days was significantly higher (i.e. cats showed fewer signs of anxiety/fear) in the alpha-casozepine group than the placebo group (p<0.01)

The change in behavioural score across the study was significantly higher in the alpha-casozepine group compared with the placebo group (p=0.003)

The number of 0 scores was significantly lower (i.e. fewer cats showed signs of severe fear/anxiety) in the alpha-casozepine group compared with the placebo group at 56 days (p=0.04)

Owner evaluations at day 56 were not statistically significant between the two groups (p=0.07)

There was no significant difference between the groups in terms of aggression (Mann Whitney U p=0.70; ANOVA p=0.46)

When focusing behaviour related to seeking out people, cats receiving alpha-casozepine were significantly more likely to seek out familiar (p=0.04) and unfamiliar (p=0.03) people than those receiving placebo

There was no statistically significant difference in fear at day 56 (p=0.09), though the change in fear across the study did differ significantly between the groups in favour of the alpha-casozepine group (p=0.01)

There was no statistically significant difference in autonomic signs at day 56 (p=0.16), though the change in autonomic signs across the study did differ significantly between the groups in favour of the alpha-casozepine group (p=0.04)

Study Weaknesses:

The aim of the study was not clearly stated

The method of randomisation was not clearly stated

A sample size calculation was not conducted and so the study may be underpowered

The behavioural scale used was not previously published and details of the method of validation of this scale were not given

It is not clear how the subjective owner assessment of improvement in behaviour was measured

It is not clear how similar the groups were in terms of breed, sex, neutering status, age, weight and environment at the start of the study, which may be important given the small sample size

A sponsor is referred to as having conducted the randomisation, the sponsor of the study and any conflict of interest is not clearly stated, though one author is an employee of Ingredia Inc who produce Zylkene

Multiple statistical comparisons were conducted, however adjustments, such as a Bonferroni correction, were not made to account for this - given that many of the p values were only just below the 0.05 cut off used, such a correction may have impacted the interpretation of the results

The authors attributed the lack of significant findings relating to aggression to the small sample size, but did not discuss the implications of this for the other results

Attachment:

Comments

It should be noted that all cats in this study also received some behavioural modification alongside the use of Zylkene or placebo. When addressing behavioural problems, it is always advisable to seek the advice of, and where appropriate, referral to, a suitably qualified behaviourist, and to ensure that any medications are used alongside appropriate behavioural modification techniques. While the results of this study do reveal some statistically significant improvements in signs of anxiety for cats receiving Zylkene, it is important to consider whether the differences observed are clinically significant, particularly given the lack of significant improvement noted by owners. The results show promise and suggest that some cats may respond well to this treatment, however given the small sample size it is unclear how representative this is of the general population. Development of a standardised, published and widely accepted tool for assessing anxiety in cats, alongside a larger randomised controlled trial to assess the efficacy of Zylkene is needed.

Bottom line

There is insufficient evidence to recommend the use of alpha-casozepine to reduce signs of anxiety/fear in cats.

Disclaimer

The BETs on this website are a summary of the evidence found on a topic and are not clinical guidelines. It
is the responsibility of the individual veterinary surgeon to ensure appropriate decisions are made based on
the specific circumstances of patients under their care, taking into account other factors such as local
licensing regulations. Read small print